Prostate-specific membrane antigen (PSMA) is an effective cell surface marker for prostatic epithelial cells and is increased in expression in prostatic cancer, particularly the more aggressive forms of the disease. We have prepared a panel of monoclonal antibodies for extracellular epitopes present on PSMA. Studies will be conducted to determine their potential suitability for in vivo targeting of therapeutics to prostatic tumors. Antigen binding affinity will be determined as will their intrinsic ability to elicit ADCC and CDC cell killing. Specificity of 125I-labeled antibody binding to PSMA expressing and non-expressing cells will be tested in vitro as well as biodistribution of labeled antibody in mice bearing tumors which are both expressors and non-expressors of PSMA. Based on these results, an initial test will be conducted to assess tumoricidal activity of a 90Y-labeled antibody in mice bearing PSMA expressing and non-expressing tumors. The results will provide definitive evidence to assess the potential of anti- PSMA antibody targeting of therapeutics in treatment of prostate cancer in humans. PROPOSED COMMERCIAL APPLICATIONS: There were 209,900 new cases of prostatic cancer diagnosed in 1997. Many of these patients have, or will develop, metastatic cancer which is resistant to presently available therapy. Application of antibody targeting of therapeutic agents to prostate cancer via markers such as prostate-specific membrane antigen should be specific and result in new means to treat advanced disease.